Fucus vesiculosus-Derived Fucoidan Mitigates Recognition Memory Deficits in Association with Modulation of the Microbiota-Gut-Brain Axis in Adenine-Induced Chronic Kidney Disease Mice.

Chronic kidney disease (CKD) induces systemic oxidative stress and inflammation, leading to secondary cognitive impairment. The mechanisms by which marine-derived fucoidan exerts neuroprotection remain incompletely understood. Here we show that oral administration of Fucus vesiculosus-derived fucoidan improved object-recognition and object-location preferential indices, attenuated renal tubulointerstitial fibrosis, and reduced systemic oxidative and inflammatory markers in adenine-induced CKD mice. In hippocampal tissue, fucoidan attenuated oxidative stress and neuroinflammation, as reflected by decreased MDA and ROS levels, improved SOD and CAT activities, reduced TNF-α and IL-1β levels, and increased IL-10 and IL-4 levels. Integrating 16S rRNA sequencing with non-targeted serum metabolomics, we show that fucoidan is associated with modulation of CKD-induced gut dysbiosis, a lower relative abundance of circulating, putatively annotated uremic-toxin features, and altered lipid and amino acid metabolic pathways. Multi-omics correlation analysis identified significant associations among specific bacterial taxa, aberrant serum metabolites, and host physiological parameters. These results indicate that the renoprotective and neuroprotective effects of fucoidan are associated with gut microbiota regulation and altered circulating uremic-toxin features, highlighting its potential as a marine-derived prebiotic for CKD-associated complications.